1. Area of the Art
The present invention relates to the art of producing coagulation factor concentrates from blood plasma.
2. Description of the Prior Art
There are a number of medical indications for administration of “clotting” or “coagulation” factors from human blood. These factors are proteins that cause the clotting of blood to staunch bleeding from wounds, etc. Individuals with any of a series of genetic abnormalities affecting the proteins responsible for blood coagulation are afflicted with a disease (hemophilia) in which the blood fails to clot normally, subjecting the individual to the danger of uncontrolled bleeding. For many years, this condition has been treated by administering concentrates of the missing or defective proteins. Many clotting factors are synthesized in the liver so that victims of liver disease are also in need of augmentation of their clotting factors.
While some of the clotting factors are currently produced by means of biotechnology, at this time there is still no cost effective method of artificially manufacturing all of these proteins or these proteins in sufficient quantities. Further, the “artificially produced” factors made by recombinant and related technologies tend to have a shorter half-life in circulation. In addition, many of the “minor” clotting factors are not yet (and may never be) available from biotechnology sources and so must be purified from donated human blood. Also, there is often a synergy between factors whereby a single administered recombinant factor may not be as effective as a natural mixed fraction fractionated from collected blood plasma. In Third World countries the biotechnology products are generally either not available or are prohibitively expensive. Therefore, much of the supply of anti-hemophilia factor (AHF, also known as Factor VIII), and other blood clotting factors are prepared from pooled human plasma in the Third World.
The basic methods for preparing clotting factor concentrates from blood have not changed greatly over the last few decades. Generally, a concentrate of clotting factors is produced from pooled plasma by an initial cryoprecipitation step. The plasma is frozen and then thawed. During the freezing process certain proteins precipitate to form a “cryoprecipitate.” Various additives such as ethanol and/or polyethylene glycol may be added to enhance the efficiency of the cryoprecipitation step. The present inventor has found that sodium citrate can advantageously used as an additive to enhance cryoprecipitate production (see U.S. Pat. No. 6,541,518 the contents of which are hereby incorporated by reference). Following cryoprecipitation, it is usual to extract clotting factors from the cryoprecipitate. The cryoprecipitate is usually extracted with water or buffer in the cold. Under such conditions clotting factors and some other proteins are dissolved out of the precipitate yielding a crude clotting factor mixture. This crude mixture is usually further purified by means of additional precipitation steps or by chromatographic methods, and most recently by methods using monoclonal antibodies. For additional information on the basic techniques of clotting factor purification and the history of the development of these methods, the reader is directed to U.S. Pat. Nos. 3,560,475, 3,631,018, 3,682,881, 4,069,216, and 4,305,871 and 5,770,704 by the present inventor, the contents of which are incorporated herein by reference, and the references cited therein.